Defining the role of lymphatic vessels in wound healing

我的实验室最近发现了淋巴管在皮肤创伤中的一个意想不到的有趣的作用 治愈。特别是，我们发现没有淋巴管的小鼠表现出血管过度再生和 损伤后的纤维化。我们的发现之所以重要，有几个原因。首先，虽然淋巴管已经 这些细胞被证明对皮肤修复很重要，但对它们在皮肤修复中的确切功能知之甚少。 其次，我们的数据显示，涉及淋巴管的未知机制控制着血管修复和 皮肤纤维化是影响伤口愈合和过度结疤的两种情况。最后，淋巴水肿，一种慢性的， 淋巴管系统受损可能导致衰弱和无法治愈的肿胀，原因是 手术、癌症、治疗或伤害影响着1000多万美国人。通过这些聚焦和 互补的特定目标，本申请中提出的工作将利用多个基因 允许特定淋巴管耗尽的小鼠模型、最先进的基因组学、细胞培养模型。 我们将(1)确定驱动淋巴管内皮细胞再生的细胞和分子机制。 皮肤，(2)分析淋巴管内皮细胞在抑制血管修复和修复中的作用 有助于纤维化，以及(3)确定加强淋巴管修复是否可以改善有缺陷的伤口 对衰老和糖尿病小鼠的影响。这些研究将确定特定的促进愈合的细胞和分子机制 可用于促进伤口愈合缺陷或淋巴疾病患者的愈合。

My laboratory recently uncovered an unexpected and intriguing role for a lymphatic vessels during skin wound healing. In particular, we identified that mice without lymphatic vessels display hypervascular regeneration and fibrosis after injury. Our findings are important for several reasons. First, while lymphatic vessels have been shown to be important for skin repair, the precise function of these cells in skin repair is poorly understood. Second, our data reveal that unknown mechanisms involving lymphatic vessels control blood vessel repair and skin fibrosis, two conditions that impact wound healing and excessive scarring. Finally, lymphedema, a chronic, debilitating and incurable swelling that can be a result of damage to the lymphatic vessel system due to surgery, cancer, treatments, or injury, affects over 10 million Americans. Through these focused and complementary Specific Aims, the work proposed in this application will take advantage of multiple genetic mouse models that allow specific depletion of lymphatic vessels, state of the art genomics, cell culture models. We will (1) identify the cellular and molecular mechanisms that drive lymphatic endothelial regeneration in the skin, (2) analyze the function of lymphatic endothelium cells in suppressing blood vessel repair and contributing to fibrosis, and (3) define whether enhancing lymphatic vessel repair ameliorates defective wounds of aged and diabetic mice. These studies will identify specific pro-healing cells and molecular mechanisms that can be utilized to promote healing in human patients with defective wound healing or lymphatic disorders.